Neuronal action potentials are electrical signals that travel along the axon to induce release of chemical neurotransmitters at synapses. However, action potentials also backpropagate into dendrites, the branching input structures of neurons. Though its role is not fully understood, backpropagation undoubtedly affects dendritic signal processing in important ways. Understanding dendritic signal processing is critical to a full understanding of normal learning and memory, which includes changes in dendrites and dendritic inputs, and diseases involving dendritic dysfunction such as epilepsy, some forms of mental retardation, Parkinson's disease, and others. This proposal explores the possibility that spike trains with realistic, irregular timing may be more effective at generating backpropagation and long term potentiation (LTP), the primary model of learning and memory, than the artificial regular spike trains that are generally used to induce it experimentally. Initial experiments will test which type of spike train stimulated in hippocampal CAI pyramidal neurons backpropagates more efficiently into the dendrite: real, irregular spike trains taken from in vivo experiments or regular spike trains of the same overall frequency. The role of various frequency components of the spike trains in backpropagation efficiency will be tested. Next calcium imaging of the CA1 dendrites will determine if real inputs result in more calcium influx, necessary to LTP induction, than artificial inputs. Lastly, LTP will be generated at the Schaffer collateral-CA1 synapse by pairing trains of subthreshold synaptic stimuli with matched spike trains in the CA1 pyramidal soma. The amount of LTP induced by real, irregular and artficial, regular spike trains will be compared. These experiments will test the hypothesis that physiological back ro a ation is more effective and supports LTP more readil than commonly-used regular stimuli.